Recirculation of fresh, heparinized human blood in an extracorporeal perfusion circuit containing a membrane oxygenator causes a decrease in platelet count to 20 percent of control within 2 minutes, loss of the ability of platelets to respond to soluble aggregating agents and a progressive increase in low affinity platelet antiheparin factor. Pre-coating the circuit with 5 percent albumin or addition of prostaglandin E1 prevents the loss of platelet numbers and function during recirculation and prevents progressive increase in low affinity platelet anti-heparin factor. Rhesus monkey platelets differ from human platelets but more closely resemble human platelets than do platelets of pig or lamb. During one hour of total cardiopulmonary bypass in rhesus monkeys platelet counts decrease to 60 percent of control, platelets are insensitive to adenosin diphosphate, and bleeding times are increased 2.4 times more than control after bypass stops, and heparin is neutralized with protamine. If PGE1 is added to priming blood and is infused during bypass (0.2 to 5 micron g/kg/min) platelet numbers and function are preserved and bleeding times do not differ from control when bypass stops. Protocols for clinical trials using albumin and/or PGE1 to preserve platelets during bypass are being reviewed.